DRUG INDUCED KIDNEY INJURY Flashcards
EPIDEMIOLOGY - read
▪ Nephrotoxic drugs were contributing factors in 19-25% of cases of severe
acute kidney injury
▪ Older adults – as high as 66%
▪ Common complication of several diagnostic and therapeutic agents
▪ Source of significant morbidity and mortalit
drugs causing Prerenal/Hemodynamic injury
ACE inhibitors/ARBs
NSAIDS
Calcineurin inhibitors
drugs causing intrinsic injury
- acute tubular necrosis
- acute interstital nephritis
- chronic interstital nephritis
Acute Tubular Necrosis
Amphotericin B
Aminoglycosides
Radiographic Contrast Dye
Penicillins
Lithium
Calcineurin inhibitors
drugs causing Obstructive (Post renal) injury
Acyclovir
Indinavir
Sulfonamide antibiotics
see slide 45 for autoregulation
ok
ACE INHIBITORS/ARBS HEMODYNAMIC (PRERENAL) RENAL FAILURE
which pts are at higher risk?
Patients at higher risk:
▪ Patients with severe atherosclerotic disease
▪ Renal artery stenosis (bilateral)
▪ Heart Failure (acute, decompensated)
▪ Chronic Kidney Disease (severe later stages)
▪ Volume depleted
Examples ▪ ACEI: Ramipril, Lisinopril, Perindopril
▪ ARBS: Telmisartan, irbesartan, valsartan
ACE INHIBITORS/ARBS HEMODYNAMIC (PRERENAL) RENAL FAILURE
presentation?
how does it work?
▪ ≥ 30% rise in serum creatinine within 2 to 7 days following initiation of therapy
▪ Usually stabilizes within 1 week
Mechanism
▪ Normally, in cases of decreased renal blood flow, intraglomerular blood pressure is maintained by vasodilation of the afferent arteriole and vasoconstriction of the efferent arteriole
▪ ACE inhibitors dilate the efferent arteriole and thus reduce glomerular hydrostatic
pressure = ↓ GFR
ACE INHIBITORS/ARBS HEMODYNAMIC (PRERENAL) RENAL FAILURE
urine findings
- volume, conc, FeNa, BUN, creatine
management?
▪ Low urine volume ▪ Low urine sodium concentration (< 20 mmol/L) ▪ FeNa <1% ▪ Urinalysis: relatively normal ▪ Specific gravity >1.010 ▪ No casts or cellular elements ▪ High BUN, High Creatinine ▪ Management ▪ d/c ACE inhibitor or ARB ▪ Supportive therapy
ACE INHIBITORS/ARBS HEMODYNAMIC (PRERENAL) RENAL FAILURE
prevention
▪ Prevention
▪ Obtain baseline SCR and K+
▪ Start with low doses, titrate dose gradually
▪ Avoid other drugs which may alter renal blood flow
▪ NSAIDS
▪ Maintain hydration
▪ Monitor SCr and K+ regularly
▪ Temporarily stop drugs in the setting of “stressed” kidneys
NSAIDS HEMODYNAMIC (PRERENAL) RENAL FAILURE
which pts at higher risk?
which NSAID will most likely impair renal fxn?
▪ Patients at higher risk: ▪ Chronic Kidney disease ▪ Heart failure ▪ Elderly ▪ ACE Inhibitor/NSAID combination
▪ Indomethacin is most likely to impair renal function
▪ Low dose Aspirin does not impair renal function!
NSAIDS HEMODYNAMIC (PRERENAL) RENAL FAILURE presentation? mechanism?
see slide 54!
Presentation
▪ Patients present with low urine volume, edema/weight gain and elevated SCr, K+,
and BUN
Mechanism
▪ In patients with altered renal perfusion, the compensatory response is to release
PGs. Inhibition of COX-2 inhibits this prostaglandin response. NSAIDS, therefore,
inhibit afferent arterial dilation and reduce GFR
NSAIDS HEMODYNAMIC (PRERENAL) RENAL FAILURE
urine findings
- volume, conc, FeNa, BUN, creatine
▪ Urine Findings ▪ Low urine volume ▪ Low urine sodium (<20mmol/L) ▪ FeNa <1% ▪ Urinalysis: relatively normal ▪ ↑ SG ▪ No casts or cellular debris
▪ High BUN, High Creatinine
NSAIDS HEMODYNAMIC (PRERENAL) RENAL FAILURE
management and prevention
▪ Management
▪ d/c offending agent
▪ Supportive therapy
▪ Prevention ▪ Avoid NSAID use in elderly, HF, CKD ▪ Avoid concomitant use with ACEI or ARB ▪ Start with low doses and titrate slowly ▪ Monitor BP, SCr, and BUN regularly
ACUTE TUBULAR NECROSIS (ATN)
▪ Most common form of intrarenal acute kidney injury.
▪ Precipitating factors include ischemic and nephrotoxic processes.
▪ Clinical course is highly variable
▪ Oliguric phase: Within 24 hours and lasting 1-3 weeks
▪ Diuretic phase: Usually indicates renal recovery
▪ Mortality rates range from 50-70%
▪ Complete recovery of renal function may not return
ATN causes
Nephrotoxic ATN ▪ Endogenous or exogenous ▪ Myoglobin ▪ Aminoglycosides (gentamicin, tobramycin) ▪ CT Contrast Dye
Sepsis associated ATN
▪ Ischemia and toxin related
ATN - AMINOGLYCOSIDES
which pts at high risk?
▪ Gentamicin, tobramycin
Patients at high risk ▪ Dehydrated ▪ Sepsis, ischemia ▪ Pre-existing renal impairment ▪ Concomitant nephrotoxins ▪ Sustained high AG serum levels and large cumulative doses ▪ Long term AG therapy (> 14 days)
Presentation
▪ ↑ SCr 6-10 days
ATN - AMINOGLYCOSIDES
mechanism
▪ Epithelial cell damage in proximal tubular cells
▪ Direct signaling of cell death of proximal tubule cells
▪ Toxicity related to cationic charge
▪ Neomycin>gentamicin/tobramycin>amikacin>streptomycin
ATN - AMINOGLYCOSIDES
urine findings
▪ Muddy brown epithelial cell casts and free epithelial cells ▪ High urine sodium (> 40 mmol/L) ▪ FeNa >3% ▪ Urinalysis ▪ Specific Gravity ~1.010
ATN - AMINOGLYCOSIDES
management and prevention
Management ▪ D/C aminoglycoside ▪ Supportive therapy ▪ Correct volume derangements ▪ Correct metabolic acidosis ▪ Hemodialysis/Renal Replacement Therapy
Prevention ▪ Avoid hypovolemia ▪ Avoid prolonged therapy ▪ Therapeutic drug monitoring ▪ Avoid other nephrotoxins ▪ Alternate dosing strategies ▪ Avoid high risk populations – elderly, pre-existing renal impairment
ACUTE INTERSTITIAL NEPHRITIS
presentation
▪ Up to 3% of all cases of acute kidney injury
Presentation ▪ Fever ▪ Rash ▪ Pyuria/hematuria ▪ Oliguria ▪ Other ▪ Metabolic acidosis ▪ Hyperkalemia ▪ Salt wasting ▪ Occur ~ 14 days after exposure to drug
ACUTE INTERSTITIAL NEPHRITIS
mechanism
▪ Hypersensitivity reaction
▪ Lymphocytic infiltration of the interstitium
ACUTE INTERSTITIAL NEPHRITIS
urine findings
implicated drugs (2)
▪ WBC (pyuria) ▪ FeNa >1% ▪ Urine Na > 40mmol/L ▪ Hematuria ▪ White cell casts ▪ Mild proteinuria ▪ Eosinophils
▪ Implicated drugs: penicillins, lithium (Chronic Interstitial Nephritis)
ACUTE INTERSTITIAL NEPHRITISS
management
▪ Management ▪ D/C offending drug ▪ Supportive therapy ▪ Correct volume derangements ▪ Prednisone therapy for up to 4 weeks ▪ Intermittent hemodialysis
OBSTRUCTIVE NEPHROPATHY
3 presentations
▪ Refers to problems in the ureters, bladder and urethra
▪ Must be in both kidneys
3 presentations
▪ Renal tubular obstruction
▪ Extrarenal urinary tract obstruction
▪ Nephrolithiasis (kidney stones)
OBSTRUCTIVE NEPHROPATHY
pts at high risk
▪ Volume depleted
▪ Underlying renal insufficiency
▪ Concomitant metabolic disorders
OBSTRUCTIVE NEPHROPATHY
explain
▪ Renal tubular obstruction
▪ Extrarenal urinary tract obstruction
▪ Nephrolithiasis (kidney stones)
which drugs cause them?
Renal Tubular Obstruction
▪ Intratubular precipitation of drug crystals or other tissue degradation products
▪ Ex: acyclovir, rhabdomyolysis with statins
Extrarenal urinary tract obstruction
▪ Males with BPH given anticholinergic drugs
Nephrolithiasis
▪ Precipitation of stone forming components into ureters
▪ Indinavir
OBSTRUCTIVE NEPHROPATHY
urine findings
management
Urine Findings ▪ Red/white blood cells ▪ Crystals ▪ Acyclovir – needle shaped ▪ Indinavir – rectangular plates or rosettes
Management ▪ d/c offending drug ▪ Hydration ▪ Loop diuretic ▪ Supportive therapy
OBSTRUCTIVE NEPHROPATHY
prevention
▪ Aggressive hydration
▪ Avoid rapid infusions and large bolus doses of acyclovir
▪ Urine alkalinization
DRUG-INDUCED STONES
risk factors
● 1-2 % of all stones ● Risk Factors ▪ Daily dose ▪ Duration of treatment ▪ Urinary excretion of drug or metabolite ▪ Solubility of drug or metabolite ▪ Concentration peaks in the urine – rate of elimination ▪ Morphology of the crystals
DRUG INDUCED STONES - CAUSES
which drug classes cause crystallization in urine?
● Crystallize in the urine
▪ Antibacterials – sulphonamides, cephalosporins, quinolones, furanes, pyridines,
aminopenicillins
▪ Protease inhibitors (indinavir, nelfinavir, acyclovir)
▪ Antihypertensives (triamterene)
▪ Others: primidone, methotrexate, guaiafenisin, allopurinol, sulfasalazine
DRUG INDUCED STONES - CAUSES
which drug classes cause metabolically induced in urine?
● Metabolically induced
▪ Change in fluid balance – furosemide, corticosteroids, laxative abuse
▪ Change pH – carbonic anhydrase inhibitors, carbonate/bicarbonates, alkalinizing agents, acidifying drugs
▪ Hypercalciuria – calcium and vitamin D supplements, furosemide,
corticosteroids
▪ Hypophosphatemia – aluminum hydroxide
▪ Hyperoxaluria – Vitamin C, urcosurics, antibacterials
